CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor–β–dependent manner

Tumor growth promotes the expansion of CD4+CD25+ regulatory T (T reg) cells that counteract T cell–mediated immune responses. An inverse correlation between natural killer (NK) cell activation and T reg cell expansion in tumor-bearing patients, shown here, prompted us to address the role of T reg cells in controlling innate antitumor immunity. Our experiments indicate that human T reg cells expressed membrane-bound transforming growth factor (TGF)–β, which directly inhibited NK cell effector functions and down-regulated NKG2D receptors on the NK cell surface. Adoptive transfer of wild-type T reg cells but not TGF-β−/− T reg cells into nude mice suppressed NK cell–mediated cytotoxicity, reduced NKG2D receptor expression, and accelerated the growth of tumors that are normally controlled by NK cells. Conversely, the depletion of mouse T reg cells exacerbated NK cell proliferation and cytotoxicity in vivo. Human NK cell–mediated tumor recognition could also be restored by depletion of T reg cells from tumor-infiltrating lymphocytes. These findings support a role for T reg cells in blunting the NK cell arm of the innate immune system

65 nm CMOS and IPD single-bit multi-path RF DAC with embedded programmable FIR filter

Une nouvelle approche de la conversion numérique analogique des signaux RF est proposée au sein d'une chaîne d'émission basée sur le principe de la modulation delta-sigma qui fournit un signal sur 1 bit à haute cadence dans le cadre de la recherche sur la radio logicielle. Le standard choisi pour démontrer ce concept est l'UMTS. La conversion numérique analogique du signal radiofréquence a été réalisée en mode tension pour des raisons d'efficacité par l'intermédiaire d'un amplificateur de puissance commuté. Afin de générer suffisamment de puissance avec les technologies submicroniques fonctionnant à faibles tensions d'alimentation, un combineur de puissance différentiel cinq voies avec des lignes de transmission à éléments localisés a été réalisé dans des technologies CMOS 65nm et IPD (Integrated Passive Devices), toutes deux développées par ST Microelectronics. Cette architecture offre en plus la possibilité de réaliser un filtre semi numérique reconfigurable qui permet de créer des zéros de transmission dans les bandes voisines du standard considéré. Les mesures réalisées sur un système comprenant le générateur numérique delta-sigma ainsi que le combineur de puissance à lignes de transmission et le filtrage numérique reconfigurable permettent de valider les différents principes développés dans cette thèse. Le combineur de puissance permet d'obtenir une puissance de 18dBm pour un signal sinusoïdal dans la bande fondamentale grâce à un gain en puissance relatif pour cinq voies de 14dB à 1.2GHz.Ln this work a novel approach to D/A conversion of RF signais is developed in the context of a transmission chain based on delta-sigma modulation, providing a very high speed 1 bit digital signal, suitable for software-defined radio (SDR). The standard chosen to demonstrate this con cep is UMTS. Digital to analogue conversion is realized here in a voltage-mode for efficiency reasons thanks to a switching Power Amplifier. ln order to provide enough power with low voltage deep-submicron technologies, a five channels differential power combiner using lumped element transmission lines has been realised in 65nm CMOS and Integrated Passive Devices (IPD) processes, both developed by ST Microelectronics. A reconfigurable semi-digital filter can be realized in the latter architecture ln order to create notches in the nearby frequency bands. Measurements are made on a full system, comprising a digital delta-sigma signal generator, a 5-path power combiner and a reconfigurable digital filtering. The 5-path power combiner allows a maximal output power for a single tone in fundamental band of 18dBm thanks to a 14dB relative power gain at 1.2GHz

Conversion N/A radiofréquence 1bit multivoies à filtrage programmable intégré en technologies CMOS 65nm et IPD

Une nouvelle approche de la conversion numérique analogique des signaux RF est proposée au sein d'une chaîne d'émission basée sur le principe de la modulation delta-sigma qui fournit un signal sur 1 bit à haute cadence dans le cadre de la recherche sur la radio logicielle. Le standard choisi pour démontrer ce concept est l'UMTS. La conversion numérique analogique du signal radiofréquence a été réalisée en mode tension pour des raisons d'efficacité par l'intermédiaire d'un amplificateur de puissance commuté. Afin de générer suffisamment de puissance avec les technologies submicroniques fonctionnant à faibles tensions d'alimentation, un combineur de puissance différentiel cinq voies avec des lignes de transmission à éléments localisés a été réalisé dans des technologies CMOS 65nm et IPD (Integrated Passive Devices), toutes deux développées par ST Microelectronics. Cette architecture offre en plus la possibilité de réaliser un filtre semi numérique reconfigurable qui permet de créer des zéros de transmission dans les bandes voisines du standard considéré. Les mesures réalisées sur un système comprenant le générateur numérique delta-sigma ainsi que le combineur de puissance à lignes de transmission et le filtrage numérique reconfigurable permettent de valider les différents principes développés dans cette thèse. Le combineur de puissance permet d'obtenir une puissance de 18dBm pour un signal sinusoïdal dans la bande fondamentale grâce à un gain en puissance relatif pour cinq voies de 14dB à 1.2GHz.Ln this work a novel approach to D/A conversion of RF signais is developed in the context of a transmission chain based on delta-sigma modulation, providing a very high speed 1 bit digital signal, suitable for software-defined radio (SDR). The standard chosen to demonstrate this con cep is UMTS. Digital to analogue conversion is realized here in a voltage-mode for efficiency reasons thanks to a switching Power Amplifier. ln order to provide enough power with low voltage deep-submicron technologies, a five channels differential power combiner using lumped element transmission lines has been realised in 65nm CMOS and Integrated Passive Devices (IPD) processes, both developed by ST Microelectronics. A reconfigurable semi-digital filter can be realized in the latter architecture ln order to create notches in the nearby frequency bands. Measurements are made on a full system, comprising a digital delta-sigma signal generator, a 5-path power combiner and a reconfigurable digital filtering. The 5-path power combiner allows a maximal output power for a single tone in fundamental band of 18dBm thanks to a 14dB relative power gain at 1.2GHz.LILLE1-Bib. Electronique (590099901) / SudocSudocFranceF

Genetic Manipulations of the Hyperthermophilic Piezophilic Archaeon Thermococcus barophilus

International audienceIn this study, we developed a gene disruption system for Thermococcus barophilus using simvastatin for positive selection and 5-fluoroorotic acid (5-FOA) for negative selection or counterselection to obtain markerless deletion mutants using single-and double-crossover events. Disruption plasmids carrying flanking regions of each targeted gene were constructed and introduced by transformation into wild-type T. barophilus MP cells. Initially, a pyrF deletion mutant was obtained as a starting point for the construction of further markerless mutants. A deletion of the hisB gene was also constructed in the UBOCC-3256 (⌬pyrF) back-ground, generating a strain (UBOCC-3260) that was auxotrophic for histidine. A functional pyrF or hisB allele from T. barophi-lus was inserted into the chromosome of UBOCC-3256 (⌬pyrF) or UBOCC-3260 (⌬pyrF ⌬hisB), allowing homologous comple-mentation of these mutants. The piezophilic genetic tools developed in this study provide a way to construct strains with multiple genetic backgrounds that will allow further genetic studies for hyperthermophilic piezophilic archaea

Prevention of central venous catheter (CVC) spesis in premature neonates: prospective evaluation of nursing techniques

info:eu-repo/semantics/nonPublishe

Development of an Effective 6-Methylpurine Counterselection Marker for Genetic Manipulation in Thermococcus barophilus

A gene disruption system for Thermococcus barophilus was developed using simvastatin (HMG-CoA reductase encoding gene) for positive selection and 5-Fluoroorotic acid (5-FOA), a pyrF gene for negative selection. Multiple gene mutants were constructed with this system, which offers the possibility of complementation in trans, but produces many false positives (<80%). To significantly reduce the rate of false positives, we used another counterselective marker, 6-methylpurine (6-MP), a toxic analog of adenine developed in Thermococcus kodakarensis, consistently correlated with the TK0664 gene (encoding a hypoxanthine-guanine phosphoribosyl-transferase). We thus replaced pyrF by TK0664 on our suicide vector and tested T. barophilus strain sensitivity to 6-MP before and after transformation. Wild-Type (WT) T. barophilus is less sensitive to 6-MP than WT T. kodakarensis, and an increase of cell resistance was achieved after deletion of the T. barophilus TERMP_00517 gene homologous to T. kodakarensis TK0664. Results confirmed the natural resistance of T. barophilus to 6-MP and show that TK0664 can confer sensitivity. This new counterselection system vastly improves genetic manipulations in T. barophilus MP, with a strong decrease in false positives to <15%. Using this genetic tool, we have started to investigate the functions of several genes involved in genomic maintenance (e.g., polB and rnhB)

Central venous catheter-related bacteraemia in critically ill neonates: Risk factors and impact of a prevention programme

Risk factors for central venous catheter (CVC)-related bacteraemia among infants admitted to a neonatal intensive care unit (NICU) were analysed and the impact of surveillance and continuing education on the incidence of this complication investigated. Among patients admitted to a NICU, CVC-related bacteraemia increased from 1/15 (7%) in 1987 to 11/26 (42%) in 1988 (P = 0.01). Coagulase-negative staphylococci isolated from bacteraemia patients showed clonal diversity by plasmid and chromosomal fingerprinting. A review of CVC care procedures suggested breaches in aseptic techniques. Catheter-care technique was revised to ensure maximal aseptic precautions, including the use of sterile gloves, gown and drapes. The new policy was promoted by a continuing education programme and regular feed-back of CVC-related bacteraemia incidence to NICU staff. In the four-year follow-up period, the attack-rate of CVC-related bacteraemia decreased to 18/156 (12%) patients [relative risk (RR): 0.27, 95% confidence interval (CI); 0.15-0.51; P < 0.001 vs the previous period]. By using the Cox's model proportional hazards, very low birth weight and the period before use of strict aseptic CVC care were found to be predictors of increased risk of catheter-related bacteraemia after adjustment for duration of catheterization. These data provide further evidence that strict aseptic precautions during the maintenance and utilization of CVC can contribute to lower the risk of catheter infection in critically ill neonates. Regular feedback of surveillance data was associated with a progressive decrease in incidence of infection, suggesting that it improved staff compliance with aseptic precautions.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Complete BAW filtered CMOS 90nm digital RF signal generator

International audienc

Natural killer cell IFN-gamma levels predict long-term survival with imatinib mesylate therapy in gastrointestinal stromal tumor-bearing patients.

International audienceClinical outcomes of gastrointestinal stromal tumor (GIST)-bearing patients treated with imatinib mesylate (IM) are variable. Other than the site of mutation within the c-kit gene, prognostic features of GIST remain undefined. IM can exhibit off-target effects such as triggering natural killer (NK) cell activity. We addressed whether NK cell functions could predict long term survival with IM. NK cell functions were followed up in 77 GIST patients enrolled onto two phase III trials. "Immunologic responders" were defined as patients whose NK cell IFN-gamma values after 2 months of IM were higher than or equal to the baseline value at entry into the trial. The prognostic effect of IFN-gamma on progression-free survival was assessed by a Wald test in a Cox regression analysis using the landmark method and stratified by trial and on the c-kit mutational status. Fifty-six patients were evaluable for the NK cell IFN-gamma responses at baseline and 2 months. Their median follow-up for progression-free survival was 3.7 years. Thirty-four of 56 patients were immunologic responders to IM. In the Cox regression analysis, immunologic responders possessed a hazard ratio of progression or death equal to 0.29 (95% confidence interval, 0.12-0.70; P = 0.006) compared with nonresponders. Kaplan-Meier 2-year survival estimates were 85% for immunologic responders and 50% for nonresponders. Moreover, the immunologic response added prognostic value to the c-kit mutation. The NK cell IFN-gamma production after 2 months of treatment could be considered an independent predictor of long term survival in advanced GISTs treated with IM